This invention relates to certain new chemical compounds. More particularly, it relates to certain derivatives of 2-[1-hydroxycyclopent-2-yl]-acetic acid .gamma.-lactone, which are useful as intermediates for the synthesis of naturally-occurring prostaglandins and certain analogues thereof.
The naturally-occurring prostaglandins are derivatives of the C-20 fatty acid 7-[2.beta.-octylcyclopent-1.alpha.-yl]heptanoic acid, which is also known as prostanoic acid and is depicted as follows: ##STR1## The naturally-occurring prostaglandins cause a wide variety of medicinally useful biological and pharmacological responses, both in vitro and in vivo, with the particular effect being determined by the precise chemical structure of the individual compound. Chemical modification of several of the naturally-occurring compounds has led to many additional derivatives (analogues), also having useful pharmacological properties. (See further: Bergstrom et al., Pharmacological Reviews, 20, 1 (1968) and Caton, Progress in Medicinal Chemistry, Butterworths Publications Ltd., London, 1971, Volume 8, page 317).
The so-called naturally-occurring prostaglandins have been isolated from a variety of mammalian sources. However, more recently, they have become available, together with a variety of analogues thereof, by total chemical synthesis from simple, readily-available, organic precursors. Although several basic synthetic routes to prostaglandin type compounds have been disclosed in the prior art, a series of publications by Corey et al. report one particular scheme which utilizes as intermediates certain bicyclic aldehydes of the formula: ##STR2## and the enantiomers thereof, wherein Q is hydrogen or a protected hydroxy group (e.g. tetrahydropyran-2-yloxy or dimethyl-t-butylsilyloxy). In one variation of the Corey et al. synthetic scheme, the said aldehyde of Formula I is condensed with a phosphonate ylid, to give a compound of the formula: ##STR3## wherein Q is as previously defined, thereby introducing the eight carbon atoms required in the C-12 side chain of the natural prostaglandins. See, for example, Corey et al., Journal of the American Chemical Society, 91, 5675 (1969); ibid, 92, 397 (1970); ibid, 93, 1490 (1971); ibid, 93, 1491 (1971); Journal of Organic Chemistry, 37, 3043 (1972); and ibid, 39, 256 (1974). The present invention provides, as intermediates both for naturally-occurring prostaglandins and their analogues, bicyclic aldehydes of the formula: ##STR4## and the enantiomers thereof, wherein Z represents a single bond or a trans double bond, and Q is hydrogen or a protected hydroxy group, such as tetrahydropyran-2-yloxy or dimethyl-t-butylsilyloxy.
Unexamined Japanese patent applications Nos. 50-18,459 and 50-18,460, published Feb. 26, 1975, disclose the preparation of compounds of the formula IV, wherein R is a protecting group easily removable under acidic conditions (e.g. tetrahydropyran-2-yl), and also the subsequent reaction of the said compounds of formula IV with alkyl Grignard reagents. However, that embodiment of the present invention which involves the preparation of the compound of formula IV, wherein R is tetrahydropyran-2-yloxy and its reaction with n-pentyl magnesium bromide, had been completed in this country prior to Feb. 26, 1975. ##STR5##